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Comment by mistercow | Hacker News Reader

So I'm not an evolutionary biologist or a doctor, and this is a heavily studied problem, so I am not going to say "they're doing it wrong." There's probably just something I'm missing, and I want to know what it is.

But the problem with drug resistance is that these bacteria strains evolve when exposed to a drug, so that the mechanism of action for the drug stops being effective. What I want to know is: why aren't we treating new infections by giving patients a drug with every (still working) mechanism of action at once, attacking the infection on multiple fronts?

Essentially you'd be massively constraining the optimization problem that evolution has to solve, and making it way more unlikely that the bacteria in the patient could acquire all of the necessary mutations before being wiped out.

So what is it about this strategy that wouldn't work? Why are doctors still just prescribing amoxicillin alone?

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I'm not an expert either, but combinations are apparently used. For example, you mention amoxicillin, which is often combined with something called clavulanic acid [1]. Another combination drug is Trimethoprim/sulfamethoxazole [2].

Some diseases, like resistant tuberculosis, are sometimes treated with antibiotic "cocktails".

The problem is that combinations of antibiotics may have cytotoxic effects even at doses lower than normally harmful. Those two combinations above are used because they are known to work in synergy, with few side effects.

Some antibiotics are not used except as a last resort precisely because they are so toxic to the human body that they might kill the host in the process of eradicating the target bacteria. In fact, antibiotics are found in nature all the time, but they tend to be too toxic to use.

[1] http://en.wikipedia.org/wiki/Amoxicillin/clavulanic_acid

[2] http://en.wikipedia.org/wiki/Trimethoprim/sulfamethoxazole

Precisely

There are some infections that call for combination therapy but it must always be done with an eye to side effects;

Effectively microbiologists work out what the 'MIC' or minimum inhibitOry concentration is, and then use that because hopefully that will be the least likely to cause other side effects, or I.e. totally obliterate the patients GI fauna which could open them up to attack by something worse

Surely the worst side effect would not be obliterating GI fauna but systemic cell death (apoptosis) or similar, though?

I don't think (not a doctor) that antibiotics can cause large scale apoptosis (except in unrealistic quantities).

Many antibiotics in a cocktail in significant dosages can cause kidney failure.

More unlikely is not 0, and you don't want to skip all the mid points and create the super bug in one treatment. Probably safe if you do this now and then, but not if it's the SOP for antibiotics.

No idea if that's why they don't do it. Side effects sounds plausible too.

Also, remember that medicine is all about postponing the inevitable. We put a ton of money into postponing a person's death. It makes sense that, if they don't have a better alternative, they would continue to use these antibiotics if they got local results even if the practice has an expiration date.

If a patient has a functioning immune system, it generally isn't necessary for antibiotics to clear the whole infection, especially if they're not in the hospital. The course will cull the infection long enough for the patient's body to acquire a sufficient degree of adaptive immunity to heal themselves completely. In some cases (tuberculosis), a typical patient's immune system can't be counted on to win, so cocktails are the norm. Bacterial resistance to antibiotics is not new; as Wiki notes, the genes are "ancient", and simply become more prevalent when antibiotics are used.

http://en.wikipedia.org/wiki/Tuberculosis_management#The_sta...

"The frequency of spontaneous mutations that confer resistance to an individual drug are well known: 1 in 10^7 for EMB, 1 in 10^8 for STM and INH, and 1 in 10^10 for RMP."

So resistance is basically everywhere -- it becomes deadly when it is concentrated.

I don't know much about bacteria and antibiotics, but the strategy you described is the reason HAART is so effective and HIV patients live much longer lives than they did even 20 years ago.

http://en.wikipedia.org/wiki/Management_of_HIV/AIDS

In two words: side effects.

Some powerful antibiotics are very toxic (e.g. liver, etc) and thus less used.

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